Critical contributions of pre-S1 shoulder and distal TRP box in DAG-activated TRPC6 channel by PIP₂ regulation.

ABSTRACT: Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂ or PIP₂) regulates the activities of numerous membrane proteins, including diacylglycerol(DAG)-activated TRPC3/6/7 channels. Although PIP₂ binding is known to support DAG-activated TRP channel activity, its binding site remains unknown. We screened for PIP₂ binding sites within TRPC6 channels through extensive mutagenesis. Using voltage-sensitive phosphatase (DrVSP), we found that Arg437 and Lys442, located in the channel's pre-S1 domain/shoulder, are crucial for interaction with PIP₂. To gain structural insights, we conducted computer protein-ligand docking simulations with the pre-S1 domain/shoulder of TRPC6 channels. Further, the functional significance of PIP₂ binding to t

SUBMITTER: Mori MX 

PROVIDER: S-EPMC9232555 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature